This invention relates to non-invasive methods for controlling cellular ionic calcium levels. More particularly, the invention describes methods for reducing or increasing blood glucose levels in living animals, including man, by cytosolic ionic calcium level control, through the application of low energy electromagnetic, electric, magnetic and ultrasonic fields.
Hyperglycemia, or as it is more commonly known, diabetes, is primarily characterized by abnormally high concentration levels of blood glucose, both under fasting and non-fasting conditions. In Type I diabetes, the abnormal glucose levels are principally due to an insufficiency of pancreatic beta cell produced insulin. Insulin is required for the rapid transfer of glucose from the blood to most cells of the body. Low insulin levels result in glucose remaining in the blood for extended time periods, leading to hyperglycemia and its complications. In Type II diabetes, sometimes called adult or obesity onset diabetes, sufficient insulin is present but glucose levels remain high for reasons as yet not generally agreed upon but believed to be due to liver/pancreas dysfunctioning.
Most of the emphasis in diabetes research to find a cure for the disease has been placed on insulin as the "star" player in the control of hyperglycemia, particularly in the case of Type I diabetes. Glucagon and somatostatin, on the other hand, seems to have been placed in secondary role in both types of diabetes. Yet, glucagon and somatostatin are key players in both types, particularly so, since glucagon is the counter control to insulin and is essential to the action of the liver controlled release of glucose. Somatostatin, on the other hand, regulates the release of both insulin and glucagon. Both of these hormones are produced in the pancreas by alpha cells and delta cells respectively.
Hypoglycemia, or low blood sugar, is the converse of diabetes. Its symptoms are primarily characterized by blood glucose levels significantly below normal prior to food ingestion. However, dysfunctioning of the pancreas and/or liver, can lead to low levels of blood glucose, which in turn can produce symptoms of lethargy, cause fainting, etc.
The use of low energy electromagnetic fields to alleviate the hyperglycemia condition has been reported in the medical and patent literature. Documented therein, are the inconsistencies and indeed opposite results often reported by researchers using electromagnetic fields indicating that whether or not an electromagnetic field will effect a change in blood glucose levels seems to depend upon field parameters. For example, W. B. Jolley et al, "Magnetic Field Effects on Calcium Efflux and Insulin Secretion in Isolated Islets of Langerhans", Bioelectromagnetics, 4, 103-106, (1983), presented data illustrating that insulin secretion of pancreatic beta cells was reduced under the influence of pulsed electromagnetic fields (200 microsecond pulses at a 4 KHertz rate with a burst duration of 4 milliseconds and a repetition rate of 15 pulses per second). Such a decrease in insulin secretion would be expected to increase blood glucose levels. On the other hand, Milch et al., "Electromagnetic Stimulation of the Rat Pancreas and the Lowering of Serum Glucose Levels", Trans. Am. Soc. Artif. Intern. Organs, 27, 246 (1981) presented data showing that blood glucose levels of chemically induced Type I diabetic rats was decreased by a very specific electromagnetic field (350 microsecond pulses at a 15 Hz repetition rate). The data presented by Findl et al. in U.S. Pat. No. 4,428,366 illustrates the finding of Milch et al.
While not agreeing on the mechanisms involved, many of the leading researchers in the field of Bioelectrochemistry/Biomagnetics agree that exogenous, i.e., externally applied, fields modify cellular calcium ion transport. A. Chiabrera et al, "Interaction Between Electromagnetic Fields and Cells: Microelectrophonetic Effects of Ligands and Surface Receptors", Bioelectromagnetics, 5, 173, (1984), in discussing their membrane receptor model of electric field/cell interactions state that they "adhere to the working hypothesis that when two or more receptors encounter each other, they form an encounter complex which appears to enhance calcium ion influx", if an endogenous or exogenous electric field is present. A. R. Liboff, "Cyclotron Resonance in Membrane Transport", in "Interactions Between Electromagnetic Fields and Cells", 281, Plenum Press, (1985), on the other hand, indicates exogenous fields cause a resonant energy transfer to potassium ion influx, which in turn causes increased calcium ion efflux via a potassium/calcium ion transmembrane exchange. S. M. Bawin et al., "Effects of Modulated VHF Fields on the Central Nervous System", Ann NY Acad. Sci., 247, 74, (1975) and "Sensitivity of Calcium Binding in Cerebral Tissue to Weak Environmental Electric Fields Oscillating at Low Frequency", Proc. Nat'l. Acad. Sci., U.S.A., 73, 1999 (1976), have experimentally verified that calcium-ion efflux from the external bilipid layers of chick cerebral hemisphere can be either enhanced or diminished, depending upon stimulation frequency, energy level and the type of stimulation, i.e., modulated RF or sinusoidal AC. E. Neumann, "Membranes and Electromagnetic Fields", 1, Abstracts, 8th Ann. Bioelectromagnetics Soc. Mtg., Madison, June (1986), states that regions adjacent to membrance surfaces are the targets of electric field effects, altering ionic diffusion. In particular, calcium ion influx is caused by an increased concentration gradient on the external bilayer due to field-membrane interactions. E. Findl, "Membrane Transduction of Low Energy Level Fields and the Ca.sup.++ Hypothesis" in "Mechanistic Approaches to Interactions of Electric and Electromagnetic Fields with Living Systems", 15-33, Plenum Pub. (1987), describes why some investigators experimentally show electromagnetic fields causing calcium ion efflux from cellular cytosols, while others show exogenous fields cause calcium influx. Basically both cytosolic influx and influx can occur. The direction of calcium flow is principally dependent upon field frequency. Certain specific frequencies (resonant frequencies) cause calcium ion influx, while other, non-resonant frequencies cause calcium ion efflux. The frequency dependence factor is the key to the control of cytosolic calcium levels and modification of functioning. By increasing or decreasing ionized cytosolic calcium levels, certain cellular functions, such as secretion of the pancreatic hormones insulin, glucagon and somatostatin, can be modulated.
The various electromagnetic fields heretofore employed by researchers has included what can be referred to as "resonant frequency electromagnetic fields" and "non-resonant frequency electromagnetic fields". By "resonant frequency electromagnetic fields", as used in the specification and appended claims, is meant any waveform, having a fundamental or modulation frequency of 15 Hertz or an odd multiple thereof, up to about the 19th harmonic, i.e., about 285 Hertz. By the term "non-resonant frequency electromagnetic fields" as used herein and the appended claims is meant any waveform, electromagnetic, electric, magnetic or ultrasonic field of any frequency (other than 15 Hertz or its odd multiples) between 0.1 and 10 KHertz. While researchers have heretofore employed both forms, i.e., the resonant and non-resonant frequency electromagnetic fields individually in attempts to control cytosolic ionic calcium levels and affect blood glucose levels, the use of either of these electromagnetic fields alone has provided less than satisfactory control of these levels.
Although emphasis has been placed herein on the use of low frequency electromagnetic fields, it should be understood that pulsed or alternating electric fields, amplitude modulated radio frequency fields and amplitude modulated ultrasonic vibrations can be used to similarly affect calcium ion cellular transport. Electric fields can be applied by direct contact of electrodes to the animal's skin or by capacitive coupling. Radio frequencies suitably amplitude modulated at resonant or non-resonant frequencies can be applied by the use of suitable antennas. Similarly, mechanically moved magnets, vibrated or otherwise caused to move at resonant or non-resonant frequencies can be used. Ultrasonic fields induce electrokinetic streaming potentials and streaming currents in living tissue and thus, when pulsed or modulated at resonant o non-resonant frequencies can also be employed.
A wide range of field strengths have been described in the technical literature to modulate calcium ion transport in biological tissue. Magnetic fields, for example, have been successfully employed from the milligauss to kilogauss range. Electric fields have ranged from microvolt/centimeter to volts/centimeter. The most effective range for fields strength appears to be in the 0.1 to 100 gauss and 0.01-10 volt/centimeter range.